Patients with systemic lupus erythematosus (SLE) make autoantibodies reactive with the cell surfaces of central nervous system (CNS) cells, and lymphocytes. Anti-lymphocyte autoantibodies are known to be highly cross-reactive with CNS cells, but as yet the molecular basis for this high degree of cross-reactivity is unknown. Some SLE patients develop cryoglobulinemia, and these SLE cryoproteins are known to contain large amounts of anti-lymphocyte autoantibody, presumably complexed with lymphocyte cell-surface amtogems/ As a means of studying these autoantibody-reactive lymphocyte cell-surface antigens, we have immunized rabbits with SLE cryoglobulins. These rabbit anti-SLE cryoglobulin sera have been shown to be reactive with the cell surfaces of both CNS cells and lymphocytes. By absorption studies it has also been shown that most of the anti-lymphocyte reactivity in these anti-sera is also reactive with CNS cells, a pattern of reactivity very similar to that seen with SLE anti-lymphocyte autoantibodies. To study the nature of rabbit anti-SLE cryoglobulin sera-reactive cell-surface molecules, we have used these anti-sera to immunoprecipitate cell surface proteins from detergent extracts of surface radioiodinated CNS cells and lymphocytes, followed by analysis on SDS-PAGE. The cell surface proteins precipitated are restricted in number, and appear to be highly antigenically cross-reactive between CNS cells and lymphocytes. To determine the molecular nature of this cross-reactivity we will analyze these immunoprecipitated molecules by a variety of serologic and physiochemical techniques. Additionally, we have found that some rabbit anti-SLE cryoglobulin sera immunoprecipitate cell surface molecules from SLE lymphocytes that are not present on normal lymphocytes. We will determine the nature of these "neo-antigens" in a similar manner.